title: The IGSF1 deficiency syndrome: characteristics of male and female patients.
abstract: BACKGROUND
  Ig superfamily member 1 (IGSF1) deficiency was recently discovered as a novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism. However, clinical and biochemical data regarding growth, puberty, and metabolic outcome, as well as features of female carriers, are scarce.
  
  
  OBJECTIVE
  Our objective was to investigate clinical and biochemical characteristics associated with IGSF1 deficiency in both sexes.
  
  
  METHODS
  All patients (n = 42, 24 males) from 10 families examined in the university clinics of Leiden, Amsterdam, Cambridge, and Milan were included in this case series. Detailed clinical data were collected with an identical protocol, and biochemical measurements were performed in a central laboratory.
  
  
  RESULTS
  Male patients (age 0-87 years, 17 index cases and 7 from family studies) showed CeH (100%), hypoprolactinemia (n = 16, 67%), and transient partial GH deficiency (n = 3, 13%). Pubertal testosterone production was delayed, as were the growth spurt and pubic hair development. However, testicular growth started at a normal age and attained macro-orchid size in all evaluable adults. Body mass index, percent fat, and waist circumference tended to be elevated. The metabolic syndrome was present in 4 of 5 patients over 55 years of age. Heterozygous female carriers (age 32-80 years) showed CeH in 6 of 18 cases (33%), hypoprolactinemia in 2 (11%), and GH deficiency in none. As in men, body mass index, percent fat, and waist circumference were relatively high, and the metabolic syndrome was present in 3 cases.
  
  
  CONCLUSIONS
  In male patients, the X-linked IGSF1 deficiency syndrome is characterized by CeH, hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight. A subset of female carriers also exhibits CeH.
authors.affiliation: MD, Department of Endocrinology and Metabolism C7-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. S.D.Joustra@lumc.nl.
authors.forename: S D
authors.initials: SD
authors.lastname: Joustra
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authors.lastname: Sun
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authors.lastname: Appelman-Dijkstra
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authors.lastname: Heinen
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authors.lastname: Pereira
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authors.lastname: Bernard
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: K
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authors.lastname: Chatterjee
authors.forename: M T
authors.initials: MT
authors.lastname: Dattani
authors.forename: W
authors.initials: W
authors.lastname: Oostdijk
authors.forename: N R
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authors.lastname: Biermasz
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
authors.forename: A S P
authors.initials: AS
authors.lastname: van Trotsenburg
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging; D002648:Child; D003409:Congenital Hypothyroidism / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005192:Family Health; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006579:Heterozygote; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency* / Q000235:genetics; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D024821:Metabolic Syndrome / Q000209:etiology; D009929:Organ Size; D011388:Prolactin / Q000097:blood; D011628:Puberty, Delayed / Q000209:etiology; D013733:Testicular Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D049951:X Chromosome Inactivation
chemical_list: C112314:IGSF1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D019382:Human Growth Hormone; D011388:Prolactin